Research Articles (Medical Microbiology)

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Twice-yearly Lenacapavir or daily F/TAF for HIV prevention in cisgender women
(Massachusetts Medical Society, 2024-10) Bekker, Linda-Gail; Das, Moupali; Karim, Quarraisha Abdool; Ahmed, Khatija; Batting, Joanne; Brumskine, William; Gill, Katherine; Harkoo, Ishana; Jaggernath, Manjeetha; Kigozi, Godfrey; Kiwanuka, Noah; Kotze, Philip; Lebina, Limakatso; Louw, Cheryl E.; Malahleha, Moelo; Manentsa, Mmatsie; Mansoor, Leila E.; Moodley, Dhayendre; Naicker, Vimla; Naidoo, Logashvari; Naidoo, Megeshinee; Nair, Gonasagrie; Ndlovu, Nkosiphile; Palanee-Phillips, Thesla; Panchia, Ravindre; Pillay, Saresha; Potloane, Disebo; Selepe, Pearl; Singh, Nishanta; Singh, Yashna; Spooner, Elizabeth; Ward, Amy M.; Zwane, Zwelethu; Ebrahimi, Ramin; Zhao, Yang; Kintu, Alexander; Deaton, Chris; Carter, Christoph C.; Baeten, Jared M.; Kiweewa, Flavia Matovu
BACKGROUND : There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women. METHODS : We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo. We assessed the efficacy of lenacapavir and F/TAF by comparing the incidence of HIV infection with the estimated background incidence in the screened population and evaluated relative efficacy as compared with F/TDF. RESULTS : Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74). Background HIV incidence in the screened population (8094 participants) was 2.41 per 100 person-years (95% CI, 1.82 to 3.19). HIV incidence with lenacapavir was significantly lower than background HIV incidence (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.04; P<0.001) and than HIV incidence with F/TDF (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.10; P<0.001). HIV incidence with F/TAF did not differ significantly from background HIV incidence (incidence rate ratio, 0.84; 95% CI, 0.55 to 1.28; P=0.21), and no evidence of a meaningful difference in HIV incidence was observed between F/TAF and F/TDF (incidence rate ratio, 1.20; 95% CI, 0.67 to 2.14). Adherence to F/TAF and F/TDF was low. No safety concerns were found. Injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.9%); 4 participants in the lenacapavir group (0.2%) discontinued the trial regimen owing to injection-site reactions. CONCLUSIONS : No participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF.
Prevalence of antimalaria drug resistance-conferring mutations associated with sulphadoxine-pyrimethamineine-resistant Plasmodium falciparum in East Africa : a systematic review and meta-analysis
(BioMed Central, 2025-04) Abebe, Wagaw; Ashagre, Agenagnew; Misganaw, Tadesse; Dejazmach, Zelalem; Kumie, Getinet; Nigatie, Marye; Jemal, Abdu; Asmare, Zelalem; Kassahun, Woldeteklehaymanot; Gedfie, Solomon; Getachew, Ermias; Gashaw, Muluken; Ayana, Sisay; Gashaw, Yalewayker; Sisay, Assefa; Tadesse, Selamyhun; Eshetu, Tegegne; Awoke, Mulat; Kassanew, Birhanu; Kidie, Atitegeb Abera; Abate, Biruk Beletew; Reta, Melese Abate
BACKGROUND : The emergence and spread of drug resistance to antimalarial drugs pose a severe threat to effective malaria control and treatment. Although sulfadoxine-pyrimethamine resistance is well-documented, it is still the drug of choice for treating intermittent resistance. Molecular markers play a crucial role in tracking and understanding the prevalence of antimalarial drug resistance. Currently, there is insufficient information on the prevalence of molecular markers associated with sulfadoxine-pyrimethamine resistance in P. falciparum. OBJECTIVE : This systematic review and meta-analysis aimed to determine the pooled prevalence of antimalaria drug resistance-conferring markers associated with sulphadoxine-pyrimethamineine in Plasmodium falciparum in East Africa. METHODS : Systematic searches was performed to retrieve articles from PubMed, Scopus, Science Direct databases, and Google Scholar search engine. Sixteen potential studies that provided important data on markers for sulphadoxine-pyrimethamineine resistance in Plasmodium falciparum were systematically reviewed and analyzed. Nine antimalarial drug resistance markers responsible for sulphadoxine-pyrimethamineine resistance in Plasmodium falciparum were extracted separately into Microsoft Excel and analyzed using STATA 17.0. The inverse of variance was done to evaluate heterogeneity across studies. A funnel plot was used to determine the presence of publication bias. A trim-and-fill-meta-analysis was carried out to generate a bias-adjusted effect estimate. A random effect model was used to determine the pooled prevalence of markers responsible for sulphadoxine-pyrimethamineine resistance. Subgroup analysis was performed based on country and year of publication. RESULTS : A total of 16 studies were included for this systematic review and meta-analysis.The molecular markers like dhfr (N51I, C59R, S108N, 108N, 59R, and I164L), and dhps (A437G, K540E, & 540E) were selected for meta-analysis. From this meta-analysis, the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhfr 108N, dhfr 59R, and dhfr I164L was 88.6%, 85.3%, 89.6%, 92.2%, 71.5%, and 3.9%, respectively. Likewise, the aggregated prevalence of dhps A437G, dhps K540E, and dhps 540E was 90.2%, 80.9%, and 91.5%, respectively. The subgroup analysis based on year of publication showed that the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhps A437G, and dhps K540E, in studies conducted 2014–2018 was 97.11%, 90.57%, 96.45%, 90.89%, and 89.45%, respectively, while it was 82.03%, 81.78%, 85.12%, 89.24%, and 73.98%, respectively, in studies conducted 2019–2023. On the other hand, country-based analysis showed that the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhps A437G, and dhps K540E, in Kenya was 85.88%, 84.02%, 86.56%, 90.7%, and 77.55%, respectively. CONCLUSIONS : This systematic review and meta-analysis reveal a high prevalence of drug resistance markers associated with sulphadoxine-pyrimethamine resistance in Plasmodium falciparum across the East African region. This underscores the significant challenges in managing malaria infections caused by Plasmodium falciparum in the region. Therefore, regular monitoring, identification, and limiting of drug-resistance markers and drug-resistant P. falciparum strains must be sustained to ensure the effectiveness of malaria treatment.
Antimicrobial resistance profile of Pseudomonas aeruginosa clinical isolates from healthcare-associated infections in Ethiopia : a systematic review and meta-analysis
(Public Library of Science, 2024-08-13) Asmare, Zelalem; Reta, Melese Abate; Gashaw, Yalewayker; Sisay, Assefa; Gashaw, Muluken; Tamrat, Ephrem; Abebe, Wagaw; Misganaw, Tadesse; Ashagre, Agenagnew; Dejazmach, Zelalem; Kumie, Getinet; Nigatie, Marye; Ayana, Sisay; Jemal, Abdu; Gedfie, Solomon; Kassahun, Woldeteklehaymanot; Kassa, Mulat Awoke; Tadesse, Selamyhun; Abate, Biruk Beletew
BACKGROUND : Antimicrobial-resistant (AMR) bacterial infection is a significant global threat to the healthcare systems. Pseudomonas aeruginosa, the leading infectious agent in the healthcare setting is now one of the major threats due to AMR. A comprehensive understanding of the magnitude of AMR, particularly highly public health important pathogens such as P. aeruginosa, is necessary for the management of infections based on local information. OBJECTIVE : This systematic review and meta-analysis aimed to determine the country-wide AMR of P. aeruginosa. METHODS : Systematic searches were performed to retrieve articles from PubMed, Scopus, Web of Science, ScienceDirect electronic databases, Google Scholar search engine, and repository registrars from 2015 to 31st December 2023. Twenty-three studies that provided important data on AMR in P. aeruginosa were systematically reviewed and analyzed to determine the country-wide magnitude of P. aeruginosa AMR profile from healthcare-associated infections. AMR of P. aeruginosa to 10 different antibiotics were extracted separately into Microsoft Excel and analyzed using STATA 17.0. Cohen’s kappa was computed to determine the agreement between reviewers, the Inverse of variance (I2) was used to evaluate heterogeneity across studies, and Egger’s test to identify publication bias. A random effect model was used to determine the pooled resistance to each antibiotic. Subgroup analysis was performed by infection type and year of publication. RESULTS : This systematic review and meta-analysis revealed that the pooled prevalence of P. aeruginosa in clinical specimens associated with HAI was 4.38%(95%CI: 3.00–5.76). The pooled prevalence of AMR in P. aeruginosa for different antibiotics varies, ranging from 20.9% (95%CI: 6.2–35.8) for amikacin to 98.72% (95%CI: 96.39–101.4) for ceftriaxone. The pooled resistance was higher for ceftriaxone (98.72%), Trimethoprim-sulfamethoxazole (75.41), and amoxicillin-clavulanic acid (91.2). In contrast relatively lower AMR were observed for amikacin (20.9%) and meropenem (28.64%). The pooled multi-drug resistance (MDR) in P. aeruginosa was 80.5% (95%CI: 66.25–93.84). Upon subgroup analysis by infection types and year of publication, P. aeruginosa isolated from healthcare-associated infections exhibited higher resistance to ceftazidime (94.72%) compared to isolates from mixed types of healthcare-associated infections (70.84%) and surgical site infections (57.84%). Antimicrobial resistance in gentamicin was higher during the periods of 2018–2020 (73.96%), while comparatively lower during 2021–2023 (42.69%) and 2015–2017 (29.82%) CONCLUSIONS : Significantly high AMR and MDR were observed from this systematic review and meta-analysis. AMR obtained from this systematic review and meta-analysis urges the need for improved infection control, antimicrobial stewardship practices, and strengthened surveillance systems to control the spread of AMR and ensure effective treatment of P. aeruginosa infections.
Metagenomics analysis of sewage for surveillance of antimicrobial resistance in South Africa
(Public Library of Science, 2024-08-26) Smith, Anthony Marius; Ramudzulu, Masindi; Munk, Patrick; Avot, Baptiste J.P.; Esterhuyse, Kerneels C.M.; Van Blerk, Nico; KwendaI, Stanford; Sekwadi, Phuti
Our 24-month study used metagenomics to investigate antimicrobial resistance (AMR) abundance in raw sewage from wastewater treatment works (WWTWs) in two municipalities in Gauteng Province, South Africa. At the AMR class level, data showed similar trends at all WWTWs, showing that aminoglycoside, beta-lactam, sulfonamide and tetracycline resistance was most abundant. AMR abundance differences were shown between municipalities, where Tshwane Metropolitan Municipality (TMM) WWTWs showed overall higher abundance of AMR compared to Ekurhuleni Metropolitan Municipality (EMM) WWTWs. Also, within each municipality, there were differing trends in AMR abundance. Notably, within TMM, certain AMR classes (macrolides and macrolides_streptogramin B) were in higher abundance at a WWTW serving an urban high-income area, while other AMR classes (aminoglycosides) were in higher abundance at a WWTW serving a semi-urban low income area. At the AMR gene level, all WWTWs samples showed the most abundance for the sul1 gene (encoding sulfonamide resistance). Following this, the next 14 most abundant genes encoded resistance to sulfonamides, aminoglycosides, macrolides, tetracyclines and beta-lactams. Notably, within TMM, some macrolide-encoding resistance genes (mefC, msrE, mphG and mphE) were in highest abundance at a WWTW serving an urban high-income area; while sul1, sul2 and tetC genes were in highest abundance at a WWTW serving a semi-urban low income area. Differential abundance analysis of AMR genes at WWTWs, following stratification of data by season, showed some notable variance in six AMR genes, of which blaKPC-2 and blaKPC-34 genes showed the highest prevalence of seasonal abundance differences when comparing data within a WWTW. The general trend was to see higher abundances of AMR genes in colder seasons, when comparing seasonal data within a WWTW. Our study investigated wastewater samples in only one province of South Africa, from WWTWs located within close proximity to one another. We would require a more widespread investigation at WWTWs distributed across all regions/provinces of South Africa, in order to describe a more comprehensive profile of AMR abundance across the country.
Prevalence of pulmonary tuberculosis among key and vulnerable populations in hotspot settings of Ethiopia. A systematic review and meta-analysis
(Public Library of Science, 2024-08-29) Reta, Melese Abate; Asmare, Zelalem; Sisay, Assefa; Gashaw, Yalewayker; Getachew, Ermias; Gashaw, Muluken; Dejazmach, Zelalem; Jemal, Abdu; Gedfie, Solomon; Kumie, Getinet; Nigatie, Marye; Abebe, Wagaw; Ashagre, Agenagnew; Misganaw, Tadesse; Kassahun, Woldeteklehaymanot; Tadesse, Selamyhun; Geteneh, Alene; Kidie, Atitegeb Abera; Abate, Biruk Beletew; Maningi, Nontuthuko Excellent; Fourie, Petrus Bernardus
BACKGROUND : Despite the decline in tuberculosis (TB) incidence across many regions worldwide, including Ethiopia, the disease remains highly concentrated among vulnerable or socially marginalized populations and in high-risk settings. This systematic review and meta-analysis aims to estimate the pooled prevalence of pulmonary tuberculosis (PTB) among key and vulnerable populations (KVPs) residing in hotspot settings in Ethiopia. METHODS : Potential papers were searched systematically in PubMed, Scopus, ScienceDirect databases, Google Scholar search engine, and institutional electronic repositories/registrars. A total of 34 potential articles that provide necessary information on the prevalence of PTB were reviewed and data were analyzed to determine the pooled prevalence of PTB among KVPs. The relevant data were recorded and analyzed using STATA 17.0. Cohen’s kappa was computed to determine the agreement between reviewers, the Inverse of variance (I2) to evaluate heterogeneity across studies, and Egger’s test to identify publication bias. A random effect model was used to determine the pooled prevalence of PTB, subgroup analysis was computed by types of hotspot settings and year of publication. RESULTS : This meta-analysis demonstrates that the pooled prevalence of PTB among populations residing in hotspot settings in Ethiopia was 11.7% (95% confidence interval (95CI): 7.97–15.43) with an I2 of 99.91% and a p< 0.001. Furthermore, the subgroup analysis unveiled the pooled prevalence of PTB among KVPs residing in different hotspot settings as follows: Prison inmates 8.8% (95CI: 5.00–12.55%), University students 23.1% (95CI: 15.81–30.37%), Refugees 28.4% (95CI: -1.27–58.15%), Homeless peoples 5.8% (95CI: -0.67–12.35%), Healthcare settings 11.1% (95CI: 0.58–21.63%), Spiritual holy water sites attendees 12.3% (95CI: -6.26–30.80%), and other high-risk settings 4.3% (95CI: 0.47–8.09%). Besides, the subgroup analysis revealed that the pooled prevalence of PTB post-2015 was 10.79% (95CI: 5.94–15.64%), whereas it stood at 14.04% (95CI: 10.27–17.82%) before 2015. CONCLUSION : The prevalence of PTB among KVPs residing in the hotspot settings in Ethiopia remains significant, with a weighted pooled prevalence of 11.7%. Thus, the national TB control programs should give due attention and appropriate control measures should be instituted that include regular systematic TB screening, compulsory TB testing for presumptive TB cases among KVPs, and tightened infection control at hotspot settings.
Tuberculin skin test surveys and the annual risk of Tuberculous infection in school children in Northern KwaZulu-Natal
(Public Library of Science, 2024-06-18) Yates, Tom A.; Cebekhulu, Siphiwe; Mthethwa, Mumsy; Fourie, Petrus Bernardus; Newell, Marie-Louise; Abubakar, Ibrahim; Tanser, Frank
Tuberculin skin test surveys in primary school children can be used to quantify Mycobacterium tuberculosis transmission at community level. KwaZulu-Natal province, South Africa, is home to 11.5 million people and suffers a burden of tuberculosis disease that is among the highest in the world. The last tuberculin survey in the province was undertaken in 1979. We performed a tuberculin skin test survey nested within a demographic and health household surveillance programme in Northern KwaZulu-Natal. We enrolled children aged between six and eight years of age attending primary schools in this community. Mixture analysis was used to determine tuberculin skin test thresholds and the Annual Risk of Tuberculous Infection derived from age at testing and infection prevalence. The Community Infection Ratio, a measure of the relative importance of within-household and community transmission, was calculated from data on tuberculin positivity disaggregated by household tuberculosis contact. Between June and December 2013, we obtained tuberculin skin test results on 1240 children. Mixture analysis proved unstable, suggesting two potential thresholds for test positivity. Using a threshold of 10mm or treating all non zero reactions as positive yielded estimates of the Annual Risk of Tuberculous Infection of 1.7% (1.4–2.1%) or 2.4% (2.0–3.0%). Using the same thresholds and including children reported to be receiving TB treatment as cases, resulted in estimates of 2.0% (1.6–2.5%) or 2.7% (2.2–3.3%). The Community Infection Ratio was 0.58 (0.33–1.01). The force of infection in this community is lower than that observed in Western Cape province, South Africa, but higher than that observed in community settings in most other parts of the world. Children in this community are commonly infected with Mycobacterium tuberculosis outside the home. Interventions to interrupt transmission are urgently needed.
Human source severe acute respiratory syndrome coronavirus 2 aerosol transmission to remote sentinel hamsters
(Oxford University Press, 2025-04) Roy, Chad J.; Barer, Michael R.; Ueckermann, Veronica; Beddingfield, Brandon; Cordier, David; Fourie, Bernard P.; Vincent, Richard; Dibobo, Sego; VanReenen, Toby; Jensen, Paul; De Kock, Oliva; De Kock, Elsabe; Nardell, Edward
BACKGROUND : Bioaerosol-mediated transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via building ventilation systems has yet to be convincingly demonstrated. We used the South African Airborne Infections Research (AIR) facility near Pretoria to study human-to-animal (H2A) transmission of SARS-CoV-2 in newly diagnosed patients. While the facility was built to study tuberculosis transmission, this was its first adaptation to study H2A virus transmission. METHODS : Patients with clinically confirmed coronavirus disease 2019 were housed for up to 4 days in in the AIR facility with continuously exhausting patient ward air to hamsters housed in animal exposure rooms. After a 3-week exposure period, animals were held for an additional week to allow for antibody development. Animal sera were analyzed for anti-spike and plaque reduction activities and lung samples for pathology. RESULTS : Seven patients provided ≥400 in-residence hours over a 17-day period. Pair-housed naive golden Syrian hamsters (n = 216) received continuous exposure to mixed patient ward exhaust. Serum analyses revealed anti-SARS-CoV-2 immunoglobulin G in 58% of animals tested. Plaque reduction assays on 7 high-titer serum samples revealed neutralizing activity. CONCLUSIONS : These results support the concept that viral bioaerosols generated from patients remain infectious over long-distance transport through a building ventilation system. The seroconversion among sentinel animals supports the long-held belief that airborne infections manifest as a stochastic rather than deterministic event that is subject to a threshold dose effect. Further confirmatory studies are necessary to characterize the relationship between the bioaerosol delivered and the infections that result in this controlled H2A transmission model.
Xpert MTB/XDR implementation in South Africa : cost outcomes of centralised vs. decentralised approaches
(International Union Against Tuberculosis and Lung Disease, 2024-05-01) Cassim, N.; Omar, Shaheed Vally; Masuku, S.D.; Moultrie, H.; Stevens, W.S.; Ismail, Farzana; Da Silva, P.
INTRODUCTION : In South Africa, Xpert® MTB/RIF Ultra (Ultra) is the recommended diagnostic assay for TB with line-probe assays for first- (LPAfl) and second-line drugs (LPAsl) providing additional drug susceptibility testing (DST) for samples that were rifampicin-resistant (RR-TB). To guide implementation of the recently launched Xpert® MTB/XDR (MTB/XDR) assay, a cost-outcomes analysis was conducted comparing total costs for genotypic DST (gDST) for persons diagnosed with RR-TB considering three strategies: replacing LPAfl/LPAsl (centralised level) with MTB/XDR vs. Ultra reflex testing (decentralised level). Further, DST was performed using residual specimen following RR-TB diagnosis. METHODS : The total cost of gDST was determined for three strategies, considering loss to follow-up (LTFU), unsuccessful test rates, and specimen volume. RESULTS : For 2019, 9,415 persons were diagnosed with RR-TB. A 35% LTFU rate between RR-TB diagnosis and LPAfl/LPAsl-DST was estimated. Unsuccessful test rates of 37% and 23.3% were reported for LPAfl and LPAsl, respectively. The estimated total costs were $191,472 for the conventional strategy, $122,352 for the centralised strategy, and $126,838 for the decentralised strategy. However, it was found that sufficient residual volume for reflex MTB/XDR testing is a limiting factor at the decentralised level. CONCLUSION : Centralising the implementation of XDR testing, as compared to LPAfl/LPAsl, leads to significant cost savings.
Global prevalence, resistance rates, and underlying resistance mechanisms of clinical Mycoplasma and Ureaplasma species
(Oxford University Press, 2025-01) Ramaloko, Winnie Thabisa; Maningi, Nontuthuko Excellent; Osei Sekyere, John
Mycoplasmas are significant pathogens in human health, implicated in a range of clinical conditions from respiratory infections to urogenital disorders. Their resistance to commonly used antibiotics poses a substantial challenge to treatment and control. This study aims to provide a comprehensive overview of the global distribution of clinical mycoplasmas, elucidate their resistance to various antibiotics, and identify the genetic and molecular mechanisms underlying their resistance. A systematic review and meta-analysis were conducted, collating data from peer-reviewed publications between 2012 and 2024. The UK (100%) and Germany (98%) reported high numbers of respiratory mycoplasmas, with 7% and 2% being resistant to macrolides. For urogenital mycoplasmas, Iceland (99%) and Estonia (94%) reported a high prevalence of Mycoplasma species, whereas the UK (85%), France (82%), and the USA (82%) reported a high prevalence of Ureaplasma species. High resistance rates in Mycoplasma and Ureaplasma have been reported in Greenland (100%) and the UK (86%), respectively. The rising resistance rates in these species underscore an urgent need for updated treatment guidelines and the development of novel therapeutic options. Our findings highlight the importance of tailored antibiotic stewardship and the potential of genomic insights in guiding effective treatment strategies.
From pregnancy to beyond : renewed emphasis on comprehensive HIV prevention in South Africa
(Lippincott Williams and Wilkins, 2025-03) Babalola, Chibuzor M.; Peters, Remco P.H.; Muzny, Christina A.; Davey, Dvora Joseph; Taylor, Christopher M.; Mdingi, Mandisa M.; Mukomana, Freedom; De Vos, Lindsey; Medina‑Marino, Andrew; Klausner, Jeffrey D
South Africa continues to document high HIV prevalence, particularly among pregnant women, highlighting significant prevention gaps. This viewpoint triangulates findings from the Sixth South African HIV Prevalence Survey, the 2022 Antenatal HIV Sentinel Survey, and our ongoing “Philani Ndiphile” trial, which is evaluating STI screening algorithms to improve pregnancy outcomes. Despite a recent national decline in antenatal HIV prevalence, the Philani trial recorded an HIV prevalence of 28.6% among pregnant women, mirroring high rates across the Eastern Cape Province. The trial cohort also revealed a significant increasing trend in HIV prevalence with age, from 6% at 18 years to 63% at 43 years, highlighting the need for age-targeted interventions in young women of childbearing age. National progress toward UNAIDS’ targets for HIV status knowledge and ART initiation is evident; however, viral suppression remains a challenge, reflected in the 20% of Philani participants newly initiated or reinitiated on ART at their first antenatal visit. Efforts to reduce new HIV infections require strengthening, as high incidence rates persist among young women and during pregnancy and postpartum. Expanding access to oral and long-acting PrEP for pregnant and postpartum women is critical. Current coverage is low, and while new options show promise, implementation guidance remains limited. Socioeconomic factors, such as poverty and intimate partner violence, exacerbate HIV risk. Comprehensive interventions, including educational and vocational support, engaging male partners, and addressing STIs are essential. Continued support from global health partnerships and innovation in prevention strategies are vital to ending the epidemic and ensuring equitable outcomes.
Molecular epidemiology and AMR perspective of diarrhoeagenic Escherichia coli in Africa
(Springer, 2024-12) Kalule, John Bosco; Bester, Linda A.; Banda, Daniel L.; Derra, Firehiwot Abera; Msefula, Chisomo; Smith, Anthony Marius; Ajayi, Abraham; Kumburu, Happiness; Kwenda, Geoffrey; Yamba, Kaunda; Mwaba, John; Fakim, Yasmina J.; Sithole, Nyasha; Kanzi, Aquillah M.; Njage, Patrick M.K.; Chikuse, Francis; Tessema, Sofonias K.; Smith, Stella I.; Foster‑Nyarko, Ebenezer
INTRODUCTION : Diarrhoeagenic Escherichia coli (DEC) persistently challenges public health in Africa, contributing substantially to the diarrhoeal disease burden. This systematic review and meta-analysis illuminate the distribution and antimicrobial resistance (AMR) patterns of DEC pathotypes across the continent. METHODS : The review selectively focused on pathotype-specific studies reporting prevalence and/or AMR of human-derived DEC pathotypes from African nations, excluding data from extra-intestinal, animal, and environmental sources and studies focused on drug and mechanism experiments. Pertinent studies were retrieved from SCOPUS, PubMed, and EBSCOhost, processed with Covidence, and screened in alignment with PRISMA guidelines. RESULTS : The reviewed studies were predominantly hospital-based (80%) and paediatric-focused (91%), with a meagre 4.4% documenting DEC outbreaks. Seven DEC pathotypes were discerned, with Enteroaggregative E. coli (EAEC) being notably prevalent (43%, 95% CI 30–55%) and Entero-invasive E. coli (EIEC) least prevalent (24%, 95% CI 17–32%). Identified non-susceptibilities were noted against essential antibiotics including ciprofloxacin, ceftriaxone, and ampicillin, while instances of carbapenem and Extended-Spectrum ß-Lactamase (ESBL) resistance were scarce. CONCLUSION : Despite sporadic data on DEC prevalence and AMR in Africa, particularly in community settings, a palpable gap remains in real-time outbreak surveillance and comprehensive data documentation. Augmenting surveillance and embracing advancements in molecular/genomic characterisation techniques are crucial to precisely discerning DEC's actual impact and resistance continuum in Africa.
Detection of the epidemic Pseudomonas aeruginosa AUST-03 (ST242) strain in people with cystic fibrosis in South Africa
(Wiley, 2024-12) Hamiwe, Thabo; White, Debbie A.; Kwenda, Stanford; Ismail, Arshad; Klugman, Susan; Van Bruwaene, Lore; Goga, Ameena Ebrahim; Kock, Marleen M.; Smith, Anthony Marius; Ehlers, Marthie Magdaleen; marthie.ehlers@up.ac.za
INTRODUCTION: Pseudomonas aeruginosa AUST-03 (ST242) has been reported to cause epidemics in people with CF (pwCF) from Australia and has been associated with multidrug resistance and increased morbidity and mortality. Here, we report an epidemic P. aeruginosa (AUST-03) strain in South African pwCF detected at a public hospital and characterize the genomic antibiotic resistance determinants. METHODS: The P. aeruginosa AUST-03 (ST242) study isolates were analysed with whole genome sequencing using the Illumina NextSeq2000 platform. Raw sequencing reads were processed using the Jekesa pipeline and multilocus sequence typing and genomic antibiotic resistance characterization was performed using public databases. Genetic relatedness between the study isolates and global P. aeruginosa ST242 from public databases was determined using a maximum-likelihood phylogenetic tree. Antibiotic susceptibility testing was performed using the disk diffusion and broth microdilution techniques. RESULTS: A total of 11 P. aeruginosa AUST-03 isolates were isolated from two children with CF. The majority (8/11) of these isolates were multidrug-resistant (MDR) or extensively drug resistant; and the multidrug efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM were the most clinically relevant antibiotic resistance determinants and were detected in all of the isolates. The study isolates were the most closely related to a 2020 P. aeruginosa AUST-03 (ST242) CF isolate from Russia. CONCLUSION: Epidemic MDR P. aeruginosa strains are present at South African public CF clinics and need to be considered when implementing segregation and infection control strategies to prevent possible spread and outbreaks.
In vitro evaluation of the binding activity of novel mouse IgG1 opsonic monoclonal antibodies to Mycobacterium tuberculosis and other selected mycobacterial species
(Elsevier, 2024-05) Nyazema, Kudzai B.; Shey, Bong-Akee; Sei, Clara J.; Peters, Remco P.H.; Maningi, Nontuthuko Excellent; Fischer, Gerald W.; Fourie, Petrus Bernardus
Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of antibodies as adjunct therapeutic agents. This study assessed the binding efficacy of two novel IgG1 opsonic monoclonal antibodies (MABs; GG9 & JG7) at 5, 10, and 25 μg/mL to live cultures of Mycobacterium tuberculosis, M. avium, M. bovis, M. fortuitum, M. intracellulare, and M. smegmatis American Type Culture Collection laboratory reference strains, as well as clinical susceptible, multidrug resistant, and extensively drug resistant M. tuberculosis strains using indirect enzyme-linked immunosorbent assays. These three MAB concentrations were selected from a range of concentrations used in previous optimization (binding and functional) assays. Both MABs bound to all mycobacterial species and sub-types tested, albeit to varying degrees. Statistically significant differences in MAB binding activity were observed when comparing the highest and lowest MAB concentrations (p < 0.05) for both MABs GG9 and JG7, irrespective of the M. tuberculosis resistance profile. Binding affinity increased with an increase in MAB concentration, and optimal binding was observed at 25 μg/mL. JG7 showed better binding activity than GG9. Both MABs also bound to five MOTT species, albeit at varied levels. This non-selective binding to different mycobacterial species suggests a potential role for GG9 and JG7 as adjunctive agents in anti-TB chemotherapy with the aim to enhance bacterial killing.
Intricate interplay of CRISPR-Cas systems, anti-CRISPR proteins, and antimicrobial resistance genes in a globally successful multi-drug resistant Klebsiella pneumoniae clone
(BMC, 2025-01) Jiang, Jianping; Cienfuegos-Galletd, Astrid V.; Long, Tengfei; Peirano, Gisele; Chu, Tingyu; Pitout, Johann D.D.; Kreiswirth, Barry N.; Chen, Liang
BACKGROUND : Klebsiella pneumoniae is one of the most prevalent pathogens responsible for multiple infections in healthcare settings and the community. K. pneumoniae CG147, primarily including ST147 (the founder ST), ST273, and ST392, is one of the most globally successful MDR clone linked to various carbapenemases. METHODS : One hundred and one CG147 strains were sequenced and additional 911 publicly available CG147 genome sequences were included for analysis. The molecular epidemiology, population structure, and time phylogeny were investigated. The virulome, resistome, and mobilome were analyzed, and the recombination in the capsular region was studied. The CRISPR-Cas and anti-CRISPR were identified. The interplay between CRISPR-Cas, anti-CRISPR, and carbapenemase-encoding plasmids was analyzed and experimentally validated. RESULTS : We analyzed 1012 global CG147 genomes, with 80.4% encoding at least one carbapenemase (NDM [529/1012, 52.3%], OXA-48-like [182/1012, 17.7%], and KPC [105/1012, 10.4%]). Surprisingly, almost all CG147 strains (99.7%, 1009/1,012) harbor a chromosomal type I-E CRISPR-Cas system, with 41.8% (423/1012) containing an additional plasmid-borne type IV-A3 CRISPR-Cas system, and both target IncF plasmids, e.g., the most prevalent KPC-encoding pKpQIL-like plasmids. We found the presence of IV-A3 CRISPR-Cas system showed a negative correlation with the presence of KPC. Interestingly, a prophage-encoding anti-CRISPR AcrIE8.1 and a plasmid-borne anti-CRISPR AcrIE9.2 were detected in 40.1% (406/1012) and 54.2% (548/1012) of strains, respectively, which displayed positive correlations with the presence of a carbapenemase. Plasmid transfer experiments confirmed that the I-E and IV-A3 CRISPR-Cas systems significantly decreased (p < 0.001) KPC-encoding pKpQIL plasmid conjugation frequencies, while the AcrIE8.1 and AcrIE9.2 significantly increased (p < 0.001) pKpQIL conjugation frequencies and protected plasmids from elimination by CRISPR-Cas I-E system. CONCLUSIONS : Our results indicated a complex interplay between CRISPR-Cas, anti-CRISPR, and mobile genetic elements that shape the evolution of CG147. Our findings advance the understanding of multi-drug resistance mechanisms and will aid in preventing the emergence of future MDR clones.
Sodium, potassium-adenosine triphosphatase as a potential target of the anti-tuberculosis agents, clofazimine and bedaquiline
(MDPI, 2024-12-04) Mmakola, Khomotso Madimetsa Shelboy; Balmith, Marissa [; Steel, Helen C.; Said, Mohamed; Potjo, Moliehi; Van der Mescht, Mieke Adri; Hlatshwayo, Nomsa; Meyer, Pieter Willem Adriaan; Tintinger, Gregory Ronald; Anderson, Ronald; Cholo, Moloko C.
Multidrug-resistant tuberculosis (MDR-TB) patients are treated with a standardised, short World Health Organization (WHO) regimen which includes clofazimine (CFZ) and bedaquiline (BDQ) antibiotics. These two antibiotics lead to the development of QT prolongation in patients, inhibiting potassium (K+) uptake by targeting the voltage-gated K+ (Kv)11.1 (hERG) channel of the cardiomyocytes (CMs). However, the involvement of these antibiotics to regulate other K+ transporters of the CMs, as potential mechanisms of QT prolongation, has not been explored. This study determined the effects of CFZ and BDQ on sodium, potassium–adenosine triphosphatase (Na+,K+-ATPase) activity of CMs using rat cardiomyocytes (RCMs). These cells were treated with varying concentrations of CFZ and BDQ individually and in combination (1.25–5 mg/L). Thereafter, Na+,K+-ATPase activity was determined, followed by intracellular adenosine triphosphate (ATP) quantification and cellular viability determination. Furthermore, molecular docking of antibiotics with Na+,K+-ATPase was determined. Both antibiotics demonstrated dose–response inhibition of Na+,K+-ATPase activity of the RCMs. The greatest inhibition was demonstrated by combinations of CFZ and BDQ, followed by BDQ alone and, lastly, CFZ. Neither antibiotic, either individually or in combination, demonstrated cytotoxicity. Molecular docking revealed an interaction of both antibiotics with Na+,K+-ATPase, with BDQ showing higher protein-binding affinity than CFZ. The inhibitory effects of CFZ and BDQ, individually and in combination, on the activity of Na+,K+-ATPase pump of the RCMs highlight the existence of additional mechanisms of QT prolongation by these antibiotics.
Spiritual holy water sites in Ethiopia : unrecognized high-risk settings for transmission of pulmonary tuberculosis
(Wiley-Hindawi, 2024-04-08) Reta, Melese Abate; Maningi, Nontuthuko Excellent; Wubetu, Gizachew Yismaw; Olorunju, Steve A.S.; Fourie, Petrus Bernardus
Ethiopia is a high-tuberculosis (TB) burden country with 157 new cases per 100,000 people, with 23,800 TB-related deaths in 2020. In Ethiopia, TB patients have different healthcare-seeking behaviors. They frequently visit spiritual places, such as holy water sites (HWSs), to seek treatment for their illness spiritually. This study examined the prevalence of pulmonary TB (PTB) and drug susceptibility profiles of Mycobacterium tuberculosis (MTB) isolates among spiritual HWS attendees in Northwest Ethiopia. A cross-sectional study was conducted from June 2019 to March 2020. Sputum samples were collected, processed, and cultured using Löwenstein-Jensen (LJ) culture medium. Second-generation line probe assays (LPAs), GenoType®MTBDRplus VER2.0 and GenoType®MTBDRsl VER2.0, were used to detect anti-TB drug-resistant isolates. STATA 17 was utilized to perform descriptive statistics, bivariate, and multivariate regression analyses. Of 560 PTB-symptomatic participants, 21.8% ((95% confidence interval (95 CI): 18.4-25.2%)) were culture-positive, resulting in a point prevalence of 1,183/100,000 attendees. Amongst HWS attendees, culture-positive TB occurred most commonly in persons 18-33 years of age (28.5% (95 CI 23.4-34.3%)). Other participant characteristics significantly associated with culture-positive PTB were as follows: rural residents (adjusted odds ratio (aOR) 2.65; 95 CI 1.38-5.10), married participants (aOR 2.43; 95 CI 1.28-4.63), family members >5 per household (aOR 1.84; 95 CI 1.04-3.24), and sharing living space (aOR 10.57; 95 CI 3.60-31.13). Also, among 438 participants followed for 12 months after showing negative TB culture results while at the HWS, 6.8% (95 CI 4.4-9.4%) developed or contracted culture-positive TB post-residency at the HWSs. Of the 122 tested isolates, 20 (16.4%) were isoniazid (INH) and/or rifampicin (RIF) resistant. Multidrug-resistant (MDR) TB was detected in 15 cases (12.3%), five of which were fluoroquinolones (FLQs) resistant. The findings from this study should raise a concern about HWSs as potential high-risk settings for TB transmission. It is recommended that appropriate control measures be instituted that include compulsory TB testing and tightened infection control at HWSs, where an increased risk exists for transmission of TB.
Genetic diversity of Mycobacterium tuberculosis strains isolated from spiritual holy water site attendees in Northwest Ethiopia : a cross-sectional study
(Elsevier, 2024-06) Reta, Melese Abate; Said, Halima M.; Maningi, Nontuthuko Excellent; Wubetu, Gizachew Yismaw; Agonafir, Mulualem; Fourie, Petrus Bernardus; u18296603@tuks.co.za
BACKGROUND : The genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains was characterized among isolates from individuals with pulmonary tuberculosis (PTB) symptoms attended holy water sites (HWSs) in the Amhara region, Ethiopia. METHODS : A cross-sectional study was done from June 2019 to March 2020 to describe the genetic diversity and drug-resistance profiles of MTBC isolates. Sputum specimens were collected and cultured in the Lowenstein-Jensen culture medium. Line Probe Assay, MTBDRplus VER 2.0, and MTBDRsl VER 2.0 were used to detect first and second-line anti-TB drug-resistance patterns. A spoligotyping technique was utilized to characterize the genetic diversity. Statistical analysis was performed using STATA 15. RESULTS : Of 560 PTB-symptomatic participants, 122 (21.8%) were culture-positive cases. Spoligotyping of 116 isolates revealed diverse MTBC sublineages, with four major lineages: Euro-American (EA) (Lineage 4), East-African-Indian (EAI) (Lineage 3), Ethiopian (ETH) (Lineage 7), East Asian (EA) (Lineage 2). The majority (96.6%) of the isolates were EA (lineage 4) and EAI, with proportions of 54.3% and 42.2%, respectively. A total of 31 spoligotype patterns were identified, 26 of which were documented in the SITVIT2 database. Of these, there were 15 unique spoligotypes, while eleven were grouped with 2-17 isolates. SIT149/T3-ETH (n = 17), SIT26/CAS1-DELHI (n = 16), SIT25/CAS1-DELHI (n = 12), and SIT52/T2 (n = 11) spoligotypes were predominant. A rare spoligotype pattern: SIT41/Turkey and SIT1/Beijing, has also been identified in North Shewa. The overall clustering rate of sub-lineages with known SIT was 76.4%. Of the 122 culture-positive isolates tested, 16.4% were resistant to rifampicin (RIF) and/or isoniazid (INH). Multidrug-resistant TB (MDR-TB) was detected in 12.3% of isolates, five of which were fluoroquinolones (FLQs) resistant. SIT149/T3-ETH and SIT21/CAS1-KILI sublineages showed a higher proportion of drug resistance. CONCLUSIONS : Diverse MTBC spoligotypes were identified, with the T and CAS families and EA (lineage 4) predominating. A high prevalence of drug-resistant TB, with SIT149/T3-ETH and CAS1-KILI sublineages comprising a greater share, was observed. A study with large sample size and a sequencing method with stronger discriminatory power is warranted to understand better the genetic diversity of circulating MTBC in this cohort of study, which would help to adopt targeted interventions.
Clostridioides difficile hypervirulent strain ST1 isolated from clinical stool specimens obtained from three Provinces in South Africa
(Elsevier, 2025-02) Shirinda, Hlambani; Smith, Anthony Marius; Prinsloo, Ben; Kock, Marleen M.; Moodley, Mishalan; Ehlers, Marthie Magdaleen; marthie.ehlers@up.ac.za
Please read abstract in the article.
CRISPR-Cas9-mediated IncF plasmid curing in extraintestinal pathogenic Escherichia coli
(American Society for Microbiology, 2024-01) Chen, Liang; Peirano, G.; Yen, Kelly; Wang, Bingjie; Terlecky, Austin; DeVinney, Rebekah; Kreiswirth, Barry N.; Pitout, Johann D.D.
IncF plasmids are commonly found in extra-intestinal pathogenic Escherichia coli (ExPEC) strains, serving as reservoirs for antimicrobial resistance (AMR) genes and virulence factors, persistently coexisting with ExPEC lineages. Multidrug-resistant (MDR) high-risk ExPEC clones, particularly ST131, ST1193, and ST410, have acquired diverse IncF plasmids over time, containing various AMR determinants, contributing significantly to their global success. However, the broader roles of these IncF plasmids in the success of MDR ExPEC clones, beyond AMR, remain elusive. In this study, we employed a novel clustered regularly interspaced short palindromic repeats–CRISPR-associated protein-9 nuclease (CRISPR-Cas9)-mediated pCasCure plasmid-curing system to precisely remove specific IncF plasmids among ExPEC clones (ST1193, ST131, and ST410). Antibiotic-resistant parent strains reverted to antibiotic-susceptible states post-curing; however, IncF plasmid curing did not show significant impact on bacterial in vitro growth and had little impact on other in vitro phenotypes, including survival in water, dry environment and biofilm production. In addition, IncF plasmid curing did not affect the conjugation frequency of KPC-producing pKpQIL plasmid. This study represents a pivotal initial step in understanding the precise roles of IncF plasmids in the success of ExPEC. Future research will be crucial in investigating their influence on cell invasion and in vivo fitness, thereby providing a more comprehensive perspective on the functions of IncF plasmids in MDR ExPEC clones. IMPORTANCE : Understanding the role of IncF plasmids in the success of drug-resistant bacteria has far-reaching implications for tackling antibiotic resistance. The study's use of a novel CRISPR-Cas9-mediated plasmid-curing system provides a precision tool for dissecting the specific impact of IncF plasmids on ExPEC clones, especially high-risk, multidrug-resistant strains like ST131, ST1193, and ST410. The study offers a crucial stepping stone for future research into understanding how these plasmids influenceinfluenceinfluencemore complex aspects of bacterial behavior, such as cell invasion and in vivo fitness.
Prevalence of intestinal parasitic infections and associated factors among food handlers in East Africa : a systematic review and meta-analysis
(Springer, 2025-01) Ashagre, Agenagnew; Misganaw, Tadesse; Abebe, Wagaw; Dejazmach, Zelalem; Amare, Gashaw Azanaw; Wondmagegn, Yenesew Mihret; Worku, Kassahun Misgana; Adugna, Adane; Ahmed, Hassen; Gedifie, Solomon; Kumie, Getinet; Nigatie, Marye; Jemal, Abdu; Kasahun, Woldeteklehaimanot; Ayana, Sisay; Asmare, Zelalem; Gashaw, Yalewayker; Getachew, Ermias; Gashaw, Muluken; Sisay, Assefa; Tadesse, Selamyhun; Abate, Biruk Beletew; Kidie, Atitegeb Abera; Reta, Melese Abate
BACKGROUND : Intestinal parasitic infections are a significant public health concern, especially among food handlers, who can transmit these infections to the public through food preparation and handling. This systematic review and meta-analysis aimed to determine the pooled prevalence and associated factors of intestinal parasitic infections among food handlers in the East African region. METHODS : A systematic review and meta-analysis on intestinal parasitic infections among food handlers involved a comprehensive search across various databases, including Scopus, PubMed, ScienceDirect, Google Scholar, and the institution’s library registers. Forty relevant articles were identified and analyzed using STATA Software version 17.0. Sensitivity analysis, publication bias assessment with Egger’s test, and the Trim-and-fill meta-analysis for bias adjustment were conducted. Heterogeneity across the studies was assessed using Cochran’s Q statistic and I2 statistics, and subgroup analysis computed for significant heterogeneity (I2 value ≥ 50%). A random effect model was used to determine the pooled prevalence of intestinal parasitic infections. RESULTS : The pooled prevalence of intestinal parasitic infections among food handlers was 32.27% (95% CI 27.90–36.65). The most prevalent parasites were Entamoeba histolytica/dispar 20.83% (95% CI 13.66–28%), Ascaris lumbricoides 13.84% (95% CI 10–17.68%), Giardia lamblia 8.55% (95% CI 6.03–11.06%), and hookworm 6.43% (95% CI 3.93–8.93%). Using a common knife for cutting raw meat (AOR = 2.27, 95% CI 1.21–4.31), food handler’s untrimmed fingernails (AOR = 2.14, 95% CI 1.50–2.78), and no hand washing practices with soap after using the toilet (AOR = 2.25, 95% CI 1.33–3.18) were associated with higher rates of intestinal parasitic infections among food handlers. CONCLUSIONS : Parasitic infections among food handlers were found to be significantly prevalent. Factors contributing to this high prevalence included food handlers’ untrimmed fingernails, poor hand hygiene practices, and using a shared knife for chopping various food items, including raw meat. These findings emphasize the need for proper personal hygiene and sanitation practices among food handlers to prevent transmitting parasitic infections to consumers.

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